Drug delivery using a sacrificial host

ABSTRACT

An implantable drug-doped component, e.g., a cochlear implant, includes host material, a host-embedded drug and a sacrificial material integrated with the host. Upon exposure of the sacrificial material to a solvent, e.g., perilymph fluid, voids in the host are created which facilitate release of the drug. The host can be, e.g., polysiloxane or silicone rubber. The sacrificial material, e.g., can be a glucose monomer, sugar, cyclodextrin, a salt, a bioresorbable material, hyaluronic acid, polyurethane, polyester, polyamide, polyvinyl alcohol, polyacrylic acid, etc. Alternatively, the sacrificial material can be the host, and can facilitate release of the drug through changing a property of the sacrificial material, e.g., by exposing the component to an ethanol wash. For a cochlear implant, e.g., the drug doped material can be applied to a non-stimulating surface of the electrode array.

FIELD

The disclosed technology relates to implantable medical devices, and inparticular to implantable medical devices used to deliver drugs.

BACKGROUND

Implantable medical devices are capable of providing a wide range ofbenefits to a patient. Traditionally, there has been interest indelivering bioactive substances or chemicals (generally and collectivelyreferred to herein as “drugs”) in conjunction with such medical devicesfor a variety of purposes. For example, in one conventional approach theimplantable medical device is coated with a bioactive substance. Inother conventional approaches various techniques for delivering drugs inliquid form to a target location in a patient from an external orimplanted reservoir.

In many conventional approaches, a bioactive substance is integratedinto the polymeric coating of the implantable medical device oraccompanying component. These and other conventional approachestypically require the incorporation of the drug into the implantablemedical device during the manufacturing process of the device. Thisrequirement introduces a number of difficult problems and challenges forthe manufacturing and sterilization processes. On the other hand, theuse of reservoirs provides significant limitations to many aspects ofthe administration of the drug therapy.

SUMMARY

The technology includes an implantable drug-doped component, e.g., acochlear implant, that includes a host material, a drug embedded in thehost material, and a sacrificial material integrated with the hostmaterial. The sacrificial material facilitates the release of theembedded drug from the drug-doped component. The sacrificial materialcan facilitate the release of the drug from the drug-doped componentthrough the creation of voids in the host material upon dissolution ofthe sacrificial material upon contact with a solvent. The contact with asolvent can be upon implant of the component in a recipient, e.g.,perilymph as the solvent. The host material can be one or more of apolysiloxane and a silicone rubber. The drug can be one or more of ananti-inflammatory, a growth factor, an antibody, an anti-oxidant, anantibiotic, and a corticosteroid. The sacrificial material can be one ormore of: a glucose monomer, a sugar, cyclodextrin, a material that is atleast one of dissolvable and re-sorbable in the environment of animplant site, a salt, a bioresorbable material, hyaluronic acid,polyurethane, polyester, polyamide, polyvinyl alcohol, and polyacrylicacid. In some embodiments, the sacrificial material is the hostmaterial, and the sacrificial material facilitates the release of thedrug from the drug-doped component through changing a property of thesacrificial material. The change in property can be brought about byexposing the drug-doped component to an ethanol wash. For a cochlearimplant comprising a drug-doped component, the drug doped material canbe applied to a non-stimulating surface of the electrode array of thecochlear implant. The drug doped material can be a physical feature ofthe stimulating medical device, such as a soft tip, a ridge, or a spine.

DESCRIPTION OF THE DRAWINGS

Embodiments of the disclosed technology are described below withreference to the attached drawings, in which:

FIG. 1 is a perspective view of an exemplary stimulating medical device,a cochlear implant, having an electrode assembly in accordance withembodiments of the present technology;

FIG. 2 is a side view of a conventional implantable component of acochlear implant;

FIG. 3 is a side view and a cross section view of a section of anelectrode assembly;

FIG. 4 is a schematic representation of a set of relationships between acarrier member, a drug, and a sacrificial material in accordance withembodiments of the present technology;

FIG. 5 is a schematic representation of a set of relationships between acarrier member, a drug, and a sacrificial material in accordance withembodiments of the present technology;

FIG. 6 is a flowchart of methods in accordance with embodiments of thepresent technology;

FIG. 7A is a view of a section of an electrode assembly with drug-dopedmaterial extending down the lateral non-stimulating surface of thecarrier member, in accordance with embodiments of the presenttechnology; and

FIG. 7B illustrates exemplary cross sections of a spine of FIG. 7A, inaccordance with embodiments of the present technology.

DETAILED DESCRIPTION

Embodiments are described herein primarily in connection with one typeof implantable medical device, a hearing prosthesis, and morespecifically a cochlear implant. Cochlear implants are hearingprostheses that deliver electrical stimulation, alone or in combinationwith other types of stimulation, to the cochlear of a recipient.Therefore, as used herein a cochlear implant refers to a device thatdelivers electrical stimulation in combination with other types ofstimulation, such as acoustic and/or mechanical stimulation.

It would be appreciated that embodiments of the present technology canbe implemented in any cochlear implant or other hearing prosthesis nowknow or later developed; including auditory brain stimulators (alsoknown as auditory brainstem implants (ABIs)). Furthermore, it would beunderstood that embodiments of the present technology can be implementedin implantable medical devices other than cochlear implants such asneurostimulators, cardiac pacemakers/defibrillators, functionalelectrical stimulators (FES), spinal cord stimulators (SCS), etc.

FIG. 1 is a perspective view of an exemplary cochlear implant 100implanted in a recipient having an outer ear 101, a middle ear 105, andan inner ear 107. Components of outer ear 101, middle ear 105, and innerear 107 are described below, followed by a description of cochlearimplant 100.

In a fully functional ear, outer ear 101 comprises an auricle 110 and anear canal 102. An acoustic pressure or sound wave 103 is collected byauricle 110 and channeled into and through ear canal 102. Disposedacross the distal end of ear cannel 102 is a tympanic membrane 104 thatvibrates in response to sound wave 103. This vibration is coupled tooval window or fenestra ovalis 112 through three bones of middle ear105, collectively referred to as the ossicles 106 and comprising themalleus 108, the incus 109, and the stapes 111. Bones 108, 109, and 111of middle ear 105 serve to filter and amplify sound wave 103, causingoval window 112 to articulate, or vibrate, in response to vibration oftympanic membrane 104. This vibration sets up waves of fluid motion ofthe perilymph within cochlea 140. Such fluid motion, in turn, activatestiny hair cells (not shown) inside of cochlea 140. Activation of thehair cells causes appropriate nerve impulses to be generated andtransferred through the spiral ganglion cells (not shown) and auditorynerve 114 to the brain (also not shown) where they are perceived assound.

Cochlear implant 100 comprises an external component 142 that isdirectly or indirectly attached to the body of the recipient, and aninternal or implantable component 144 that is temporarily or permanentlyimplanted in the recipient. External component 142 typically comprisesone or more sound input elements, such as microphone 124 for detectingsound, a sound processing unit 126, a power source (not shown), and anexternal transmitter unit 128. External transmitter unit 128 comprisesan external coil 130, and preferably, a magnet (not shown) secureddirectly or indirectly to external coil 130. Sound processing unit 126processes the output of microphone 124 that is positioned, in thedepicted embodiment, by auricle 110 of the recipient. Sound processingunit 126 generates encoded signals, sometimes referred to herein asencoded data signals, which are provided to external transmitter unit128 via a cable (not shown).

Internal component 144 comprises an internal receiver unit 132, astimulator unit 120, and an elongate stimulating lead assembly 118.Internal receiver unit 132 comprises an internal coil 136, andpreferably, a magnet (also not shown) fixed relative to the internalcoil. Internal receiver unit 132 and stimulator unit 120 arehermetically sealed within a biocompatible housing, sometimescollectively referred to as a stimulator/receiver unit. Internal coil136 receives power and stimulation data from external coil 130, as notedabove. Elongate stimulating lead assembly 118 has a proximal endconnected to stimulator unit 120, and extends through mastoid bone 119.Lead assembly 118 has a distal region, referred to as electrode assembly145, implanted in cochlea 140. As used herein the term “stimulating leadassembly,” refers to any device capable of providing stimulation to arecipient, such as, for example, electrical or optical stimulation.

Electrode assembly 145 may be implanted at least in basal region 116 ofcochlea 140, and sometimes further. For example, electrode assembly 145may extend towards apical end of cochlea 140, referred to as cochleaapex 134. Electrode assembly 145 may be inserted into cochlea 140 via acochleostomy 122, or through round window 121, oval window 112, and thepromontory 123 or opening in an apical turn 147 of cochlea 140.

Electrode assembly 145 has disposed therein or thereon a longitudinallyaligned and distally extending array 146 of electrode contacts 148,sometimes referred to as electrode array 146 herein. Throughout thisdescription, the term “electrode array” means a collection of two ormore electrode contacts, sometimes referred to simply as contactsherein. As used herein, electrode contacts or other elements disposed ina carrier refer to elements integrated in, positioned on, or generallyattached to the carrier member. As such, electrode array 146 is referredto herein as being disposed in electrode assembly 145. Stimulator unit120 generates stimulation signals which are applied by electrodes 148 tocochlea 140, thereby stimulating auditory nerve 114.

In cochlear implant 100, external coil 130 transmits electrical signals(i.e., power and stimulation data) to internal coil 136 via a radiofrequency (RF) link. Internal coil 136 is typically a wire antenna coilcomprised of multiple turns of electrically insulated single-strand ormulti-strand platinum or gold wire. The electrical insulation ofinternal coil 136 is provided by a flexible silicone molding (notshown). In use, implantable receiver unit 132 may be positioned in arecess of the temporal bone adjacent auricle 110 of the recipient.

As noted, FIG. 1 illustrates a context of the present technology inwhich cochlear implant 100 includes an external component 142. It wouldbe appreciated that in alternative embodiments, cochlear implant 100comprises a totally implantable prosthesis that is capable of operating,at least for a period of time, without the need of an externalcomponent. In such embodiments, all components of cochlear implant 100are implantable, and the cochlear implant operates in conjunction withexternal component 142.

FIG. 2 is a simplified side view of an embodiment of internal component144, referred to herein as internal component 244. As shown in FIG. 2,internal component 244 comprises a stimulator/receiver unit 202, which,as described above, receives encoded signals from an external componentof the cochlear implant. Connected to stimulator/receiver unit 202 is astimulating lead assembly 250. Stimulating lead assembly 250 terminatesin an electrode assembly 218 that comprises a proximal region 210 and anintra-cochlear region 212. Intra-cochlear region 212 is configured to beimplanted in the recipient's cochlea and has disposed thereon an array246 of electrode contacts 248. Proximal region 210 is configured to bepositioned outside of the recipient's cochlea.

In certain embodiments, electrode assembly 218 is configured to adopt acurved configuration during or after implantation into the recipient'scochlea. To achieve this, in certain embodiments, electrode assembly 218is pre-curved to the same general curvature of a cochlea. In suchembodiments, electrode assembly 218 is referred to as perimodiolarelectrode assembly that is held straight by, for example, a stiffeningstylet (not shown), which stylet is removed during implantation so thatthe electrode assembly may adopt its curved configuration when in thecochlea. Other methods of implantation, as well as other electrodeassemblies that adopt a curved configuration, may be used in embodimentsof the present technology.

In other embodiments, electrode assembly 218 is a non-perimodiolarelectrode assembly that does not adopt a curved configuration. Forexample, electrode assembly 218 may comprise a straight electrodeassembly or a mid-scala assembly that assumes a mid-scala positionduring or following implantation.

In the illustrative embodiments of FIG. 2, stimulating lead assembly 250further comprises a helix region 204 and a transition region 206connecting stimulator/receiver unit 202 to electrode assembly 218. Helixregion 204 prevents the connection between stimulator/receiver 202 andelectrode assembly 218 from being damaged due to movement of internalcomponent 244 which may occur, for example, during mastication.

There have been a number of proposals for delivering drugs to an implantsite. Successful delivery of drugs to an implant site can providebenefits such as: faster recovery at the implant trauma, an increase instimulation effectiveness (e.g., by supporting hair cell survival andgrowth in cochlear implants), directly targeting diseases such astinnitus, promoting acceptance of the implant at the site, andfacilitating the function of the implant. Drug delivery to a cochlearimplant site can be achieved, inter alia, through embedding a portion ofthe implant, e.g., the electrode assembly, with the drug. As usedherein, the term “drug” includes, but is not limited to, therapeutic,prophylactic, and diagnostic agents.

Many implants, e.g., cochlear implants, employ structural elements thatare intended to remain in a recipient for the long term. As such, thesestructural elements are typically more hydrophobic than not, and arerequired to maintain structural integrity over the long term. Forexample, silicone rubber, typically used as a structural element in suchdevices, is hydrophobic in nature, and this is a significant impedimentto complete drug release in the short term from a silicone rubber/drugmix. In particular, short-term (e.g., 29 days or less) drug deliveryfrom devices intended to implanted for the long term has provedchallenging.

Embodiments of the present technology employ a sacrificial material witha drug, in combination with a host material (e.g., the carrier member310 of the electrode assembly, or at least a portion of the outer layerof the receiver/stimulator unit) to form a drug doped material. Usingthe combination of the sacrificial material, drug, and host material canmodify the characteristics of the aggregate material (e.g., the carriermember 310) and enhance drug bioavailability.

FIG. 3 shows an end section of a typical electrode assembly 345comprising an elongate electrode carrier member 310 having a pluralityof electrode contacts 348 mounted thereon. This particular electrodeassembly 345 defines a lumen 320 (shown in cross-section A-A) that,prior to insertion of the assembly 345 into the cochlea, can receive asubstantially straight stylet. Such a stylet typically has a stiffnessthat is sufficient to retain the assembly 345 in a straightconfiguration. Other electrode assemblies may be used in embodiments ofthe present technology. Conductive pathways 330 are shown in the crosssection of the electrode assembly 345. Each conductive pathway 330 istypically connected to a contact 348.

The carrier member 310 is a structural element of the electrode assembly345, and is typically made from a hydrophobic material such as medicalgrade silicone. The carrier member 310 can be made from any number ofpolysiloxanes, for example, silicone rubber Med 4860 available fromNusil.

Some embodiments of the technology are referred to herein as“void-creating” embodiments.

Referring to FIG. 4, in some void-creating embodiments 400 of thetechnology, the drug 410 and a sacrificial material 420 are combined andadded to the host material 430 of the carrier member 310. Elution of thedrug through the host material 430 is facilitated by voids in hostmaterial 430 created when the sacrificial material has been sacrificed,e.g., by exposure to one or more of a solvent, eluent, heat, orelectromagnetic field. Voids decrease the time required for a sufficientproportion of the drug to enter the body surrounding the implant withless drug residue remaining in the electrode assembly, thereforeincreasing the amount of drug available for its intended purpose.

In some void-creating embodiments, the sacrificial material can be aglucose monomer, or sugar, e.g., cyclodextrins, sometimes calledcycloamyloses, that are produced from starch by means of enzymaticconversion. Such materials are used in food, pharmaceutical, andchemical industries, as well as agriculture and environmentalengineering. The sacrificial material can be any number of natural orsynthetic agents which dissolve or re-sorb, including but not limited tosalts. The sacrificial material also can be a bioresorbable materialsuch as hyaluronic acid, poly-vinyl alcohol (PVA), poly acrylic acid(PAA), polyurethanes, polyesters, polyamides among others.

Referring to FIG. 5, in some void-creating embodiments 400 of thetechnology, the drug 430 can be coated in the sacrificial material 420and elution can occur by the drug 430 leaving the host material 430 asthe sacrificial material 420 dissolves.

Without being bound by theory, it is believed that combining the drugwith a sacrificial material in the largely hydrophobic carrier bodyallows the drug to elute through the carrier body in less time than itotherwise would based at least in part on voids created when thesacrificial material leaves the bulk material.

In some embodiments of the technology, referred to herein as “wash”embodiments, the drug-doped material is exposed, e.g., via dipping orthrough a wash, to a substance that improves the drug doped material'sability to release the drug. Without being bound by theory, it isbelieved that washing a drug-doped component in a wash such as thosedescribed herein, allows the drug to elute through the drug-dopedmaterial in less time than it otherwise would, based on the washbreaking oligomers of the host material.

In some wash embodiments of the technology, a drug-dope device (or atleast the regions of the device carry the drug) is dipped in a wash,e.g., an ethanol wash, for a suitable period of time. This step can beperformed during manufacturing, soon after manufacture of the device, orjust prior to insertion of the device.

In some embodiments of the technology, the area of drug application islimited. Limiting the area of application of the drug doped material canassist in maintaining the integrity of the carrier member 410 afterrelease of the drug has taken place. It is likely that after release ofthe drug from the drug doped material, voids would be left within thebulk material of the carrier member. These voids could result innegative effects, for example, allow for an ionic path for fluids toaccess the conductive pathway insulation and joins of conductingpathways to stimulating contacts. The voids may also impact upon thebulk material acting as a retention mechanism for the stimulatingcontacts within the carrier member 410. The voids could also causedelaminating of bulk material layers during a multiple moldingprocesses. Limiting the area of application for the drug doped materialwould avoid these issues.

Referring to FIG. 7A, a section 700 of an electrode assembly with thedrug-doped material extending down the lateral non-stimulating surface(surface 720) of the carrier member 710 away from the contacts 740, forexample, in the form of a spine 730. The drug-doped material also mayexist as a feature of the carrier member 710, for example, in the formof a soft tip 750, among others. FIG. 7B illustrates exemplary crosssections of such a spine 730 a, 730 b, 730 c, and 730 d.

The drug can be an anti-inflammatory such as Dexamethasone. Other drugsthat could be applied using this technique could include growth factors,antibodies, anti-oxidants, anti-inflammatory, antibiotics,corticosteroid etc, as applicable.

The technology includes methods of delivering a drug to an implant site.As an exemplary method, consider delivery of a drug to the implant siteof a cochlear implant electrode assembly using any one of the devicesdescribed herein. In such method, as illustrated in FIG. 6, acochleostomy is formed 610. The device (as described above to containthe drug) is inserted through the cochleostomy 620. The drug is one orboth of allowed and caused to be released from the drug-doped electrodeassembly 630. Methods for allowing or causing the drug to be releasedfrom the drug-doped assembly containing sacrificial material includeexposing the one or more of: a solvent or eluent such as perilymphfluid; heat (such as the recipient's body heat); an electromagneticfield; and a vibration, sonic, or ultrasound force.

While various embodiments of the present invention have been describedabove, it should be understood that they have been presented by way ofexample only, and not limitation. It will be apparent to persons skilledin the relevant art that various changes in form and detail can be madetherein without departing from the spirit and scope of the invention.Thus, the breadth and scope of the present invention should not belimited by any of the above-described exemplary embodiments, but shouldbe defined only in accordance with the following claims and theirequivalents. All patents and publications discussed herein areincorporated in their entirety by reference thereto.

1. An implantable drug-doped component comprising: a host material, adrug embedded in the host material, and a sacrificial materialintegrated with the host material; wherein the sacrificial materialfacilitates the release of the embedded drug from the drug-dopedcomponent.
 2. The implantable drug-doped component of claim 1 wherein:the sacrificial material facilitates the release of the drug from thedrug-doped component through the creation of voids in the host materialupon dissolution of the sacrificial material upon contact with asolvent.
 3. The implantable drug-doped component of claim 2 wherein: thesolvent is perilymph fluid.
 4. The implantable drug-doped component ofclaim 2 wherein: the contact with a solvent is at least one of: duringsurgery, and upon implant of the component in a recipient.
 5. Theimplantable drug-doped component of claim 2 wherein: the host materialis a polysiloxane.
 6. The implantable drug-doped component of claim 2wherein: the host material is a silicone rubber.
 7. The implantabledrug-doped component of claim 2 wherein: the drug at least one materialfrom the group comprising: an anti-inflammatory, a growth factor, anantibody, an anti-oxidant, an antibiotic, and a corticosteroid.
 8. Theimplantable drug-doped component of claim 2 wherein: the sacrificialmaterial is at least one of: a glucose monomer, a sugar.
 9. Theimplantable drug-doped component of claim 2 wherein: the sacrificialmaterial is a cyclodextrin.
 10. The implantable drug-doped component ofclaim 2 wherein: the sacrificial material is a material that is at leastone of dissolvable and re-sorbable in the environment of an implantsite.
 11. The implantable drug-doped component of claim 2 wherein: thesacrificial material is a salt.
 12. The implantable drug-doped componentof claim 2 wherein: the sacrificial material is a bioresorbablematerial.
 13. The implantable drug-doped component of claim 2 wherein:the sacrificial material is at least one material from the groupcomprising: hyaluronic acid, polyurethane, polyester, polyamide,polyvinyl alcohol, and polyacrylic acid.
 14. The implantable drug-dopedcomponent of claim 1 wherein: the sacrificial material facilitates therelease of the drug from the drug-doped component through changing aproperty of the sacrificial material.
 15. The implantable drug-dopedcomponent of claim 14 wherein: the change in property has been broughtabout by exposing the drug-doped component to an ethanol wash.
 16. Acochlear implant comprising: an electrode array comprising a most basalelectrode contact; and a drug-doped component comprising: a hostmaterial, a drug embedded in the host material, and a sacrificialmaterial integrated with the host material; wherein the sacrificialmaterial facilitates the release of the embedded drug from thedrug-doped component.
 17. The cochlear implant of claim 16 wherein: thesacrificial material facilitates the release of the drug from thedrug-doped component through the creation of voids in the host materialupon dissolution of the sacrificial material upon contact with asolvent.
 18. The cochlear implant of claim 17 wherein: the solvent isperilymph fluid.
 19. The cochlear implant of claim 17 wherein: thecontact with a solvent is at least one of: during surgery, and uponimplant of the component in a recipient.
 20. The cochlear implant ofclaim 17 wherein: the host material is a polysiloxane.
 21. The cochlearimplant of claim 17 wherein: the host material is a silicone rubber. 22.The cochlear implant of claim 17 wherein: the drug at least one materialfrom the group comprising: an anti-inflammatory, a growth factor, anantibody, an anti-oxidant, an antibiotic, and a corticosteroid.
 23. Thecochlear implant of claim 17 wherein: the sacrificial material is atleast one of: a glucose monomer, a sugar.
 24. The cochlear implant ofclaim 17 wherein: the sacrificial material is a cyclodextrin.
 25. Thecochlear implant of claim 17 wherein: the sacrificial material is amaterial that is at least one of dissolvable and re-sorbable in theenvironment of an implant site.
 26. The cochlear implant of claim 17wherein: the sacrificial material is a salt.
 27. The cochlear implant ofclaim 17 wherein: the sacrificial material is a bioresorbable material.28. The cochlear implant of claim 17 wherein: the sacrificial materialis at least one material from the group comprising: hyaluronic acid,polyurethane, polyester, polyamide, polyvinyl alcohol, and polyacrylicacid.
 29. The cochlear implant of claim 17 wherein: the sacrificialmaterial facilitates the release of the drug from the drug-dopedcomponent through changing a property of the sacrificial material. 30.The cochlear implant of claim 29 wherein: the change in property hasbeen brought about by exposing the drug-doped component to an ethanolwash.
 31. The cochlear implant of claim 17 wherein: the drug dopedmaterial is applied to a non-stimulating surface of the electrode array.32. The cochlear implant of claim 17 wherein: the drug-doped material isa physical feature of the stimulating medical device.
 33. The cochlearimplant of claim 17 wherein: the drug-doped material is one physicalfeature from the group of physical features comprising: a soft tip, aridge, and a spine.
 34. The cochlear implant of claim 17 wherein: thedrug-doped material is not applied on the basal side of the most basalelectrode contact.